首页> 美国卫生研究院文献>The Yale Journal of Biology and Medicine >Focus: The Aging Brain: Amyloid-beta Alzheimer targets — protein processing lipid rafts and amyloid-beta pores
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Focus: The Aging Brain: Amyloid-beta Alzheimer targets — protein processing lipid rafts and amyloid-beta pores

机译:重点:老化的大脑:淀粉样β老年痴呆症的目标-蛋白质加工脂质筏和淀粉样β孔

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摘要

Amyloid beta (Aβ), the hallmark of Alzheimer’s Disease (AD), now appears to be deleterious in its low number aggregate form as opposed to the macroscopic Aβ fibers historically seen postmortem. While Alzheimer targets, such as the tau protein, amyloid precursor protein (APP) processing, and immune system activation continue to be investigated, the recent discovery that amyloid beta aggregates at lipid rafts and likely forms neurotoxic pores has led to a new paradigm regarding why past therapeutics may have failed and how to design the next round of compounds for clinical trials. An atomic resolution understanding of Aβ aggregates, which appear to exist in multiple conformations, is most desirable for future therapeutic development. The investigative difficulties, structures of these small Aβ aggregates, and current therapeutics are summarized in this review.
机译:淀粉样蛋白β(Aβ)是阿尔茨海默氏病(AD)的标志,现在看来,它的低聚集体形式具有有害性,而与历史上验尸后的宏观Aβ纤维相反。尽管阿尔茨海默病的目标蛋白(例如tau蛋白,淀粉样蛋白前体蛋白(APP)加工和免疫系统激活)仍在继续研究中,但最近发现淀粉样蛋白β聚集在脂质筏上并可能形成神经毒性毛孔,这导致了关于为什么原因的新范式过去的治疗方法可能会失败,以及如何为临床试验设计下一轮化合物。对Aβ聚集体的原子分辨率理解(似乎以多种构象存在)是未来治疗发展中最需要的。本文综述了这些小的Aβ聚集体的研究难度,结构以及当前的治疗方法。

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